Clinical Risk And Serum Inflammatory Markers In Predicting Late Restenosis After Coronary Stent Placement And Its Mechanism Of Inflammation

Background:Stent implantation in human coronary arteries, initiated in 1986 by Sigwart et al. is intended to reduce coronary restenosis. However still high restenosis about 10-60% existed, limiting its effect. Stimuli are disruption of the endothelial barrier layer as well as mechanical stretch and disruption of media and adventitia, inducing the local inflammatory response and initiating the process of restenosis. Objectives:1 .To evaluate the predictive value of clinical influence on 6 month clinical and angiographic in-stent restenosis after coronary stent placement.2.(1) to investigate whether early and late outcome after PCI(Percutaneous coronary intervention) could be predicted by baseline levels of interleukin-6(IL-6) and c reactive protein(CRP). (2) to evaluate the magnitude of CRP or IL-6 release during the serial time point of PCI procedure in accordance with later restenosis. (3) to investigate whether nuclear factor kappa B(NF-KB) might be involved in the mechanism of development of unstable angina pectoris(UAP) and in-stent restenosis.3. (1)To study the possibility that the genetypes of the RAS gene might influence the restenosis after coronary stent placement. (2) To evalute the role of ACE I/D, AT1R A1166C gene variance on LV remodeling in patients with history of myocardial infarction. Methods:1.Patients who underwent successful coronary stenting were taken reangiography within 6-month follow-up period. (Because larger part of patients in our study had recurrence of angina with less part of patients remaining angina-free, we had much higher incidence of in-stent restenosis than that it actually had). Clinical factors (age, gender,coronary risk factors, serum levels of lipids and lipoprotein), quantitative angiographic factors(lesion localization, morphology, pre- and postangioplastic minimal lumen diameter, reference diameter, and percent diameter stenosis), together with the clinical performance of unstable angina and its risk classification were analyzed by univariate and multivariate logistic regression analysis.2. (1) restenosis model was established in the iliac artery of Chinese minipigs using balloon over stretched injury. 20 Gy dose of radiation was targeted at the injured iliac segments in experimental group while no dose of radiation used in control groups. All pigs were examined with angiography. Histologic and morphological study was done at different time point after the procedure. (2) Serum levels of CRP and IL-6 were measured in 100 coronary de novo patients undertaking stent placement containing 42 stable angina pectoris (SAP) and 58 UAP, while 51 angiographic normal patients as control groups. A coronary angiogram (CAG) was done 6 months later to determine the in-stent restenosis. (3) Circulating CRP, IL-6 and Tnl were measured at such serial period : immediately before PCI, 4 hour, 1st, 2nd and 3rd day after PCI in 35 SAP patents whose baseline CRP level before PCI or CAG was within normal range, and 20 SAP patients were taking as control group receiving only CAG examination. (4) the activity of NF-KB from peripheral blood mononuclear cells (PBMCs) was tested with electrophoresis mobility shift assay (EMSA) in UAP and SAP patients. The activity alteration of NF-KB during the period of pre-stenting and the following day after PCI was determined in 5 SAP patients, and 2 patients with only CAG was taken as control.3. (1) 102 patients with successfully stent placement were included in our study, in whom ACE I/D, AT1R A1166C and AGT M235T genotype were determined by the polymerase chain reaction (PCR) and restriction fragment length polymorphism(RFLP). Quantitative coronary angiography was performed before, immediately after and 6 months after stent implantation. Logistic regression analysis was used to determine whether the RAS gene polymorphism was related to in-stent restenosis. (2). RAS gene polymorphism distribution were comparedbetween patients with ACS and patients with normal CAG(control groups) to find genotype DD of ACE b...